Monovision and cataract surgery Visual field and OCT correlation ...

POSSIBLE MECHANISMS OF RETINAL FUNCTION RECOVERY WITH THE USE OF CELL THERAPY WITH BONE MARROW- DERIVED STEM CELLS
matrix proteins such as collagen type I, collagen type III, and
TIMP-1 which result in positive remodeling and function (25,35) .
B5) ACTIVATION OF NEIGHBORING RESIDENT STEM CELLS
Finally, exogenous stem cell transplantation may activate
neighboring resident tissue stem cells. Recent work demonstrated
the existence of endogenous, stem cell-like populations
in adult heart, liver, brain, and kidney (33-39) .
These resident stem cells may possess growth factor receptors
that can be activated to induce their migration and
proliferation and promote both the restoration of dead tissue
and the improved function in damaged tissue. Mesenchymal
stem cells have also released HGF and IGF-1 in response to injury
and when transplanted into ischemic myocardial tissue may
activate subsequently the resident cardiac stem cells.
Although the definitive mechanisms for protection via
stem cells remains unclear, stem cells mediate enhanced angiogenesis,
suppression of inflammation, and improved function
via paracrine actions on injured cells, neighboring resident
stem cells, the extracellular matrix, and the infarct zone.
Improved understanding of these paracrine mechanisms may
allow earlier and more effective clinical therapies (25,36-37) .
C) RETINAL PIGMENT EPITHELIUM (RPE) REPAIR WITH BM
DERIVED STEM CELL
RPE dysfunction has been linked to many devastating eye
disorders, including age-related macular degeneration, and to
hereditary disorders, such as Stargardt disease and retinitis
pigmentosa (38-40) . Attempts to repair the RPE include transplantation
of RPE cells into the subretinal space (39-44) . Animal studies,
RPE transplantation in humans, and macular relocation surgery
have all shown that replacing diseased RPE with healthier RPE
can rescue photoreceptors, prevent further visual loss, and even
promote visual (45) . Also, recent work on human RPE patch graft
transplantation demonstrates survival and rescue of photoreceptors
for a substantial time after grafting and holds some
promise (38) . Rescue of RPE and photoreceptors beyond the area
of donor cell distribution suggests that diffusible factors are also
involved in the rescue process. However, some problems exist,
including the ability to obtain an adequate source of autologous
RPE and that homologous cells have been associated with
rejection. Fetal or adult transplanted RPE cells attach to Bruch’s
membrane with poor efficiency and do not proliferate. These
transplantation procedures are complex, associated with high
complication rates, and often result in only short-term (45) .
Recently, it has been reported that the bone marrowderived
cells regenerated RPE in two different acute injury
models (39-44,46-48) .
Based on the above mentioned mechanisms, experimental
and human studies with intravitreal bone-marrow derived
stem cells have begun (Table 1).
Recently, some reports demonstrated the clinical feasibility
of intravitreal administration of autologous bone marrowderived
mononuclear cells (ABMC) in patients with advanced
degenerative retinopathies (49-52) . More recently, our group
conducted a prospective phase I trial to investigate the safety
of intravitreal ABMC in patients with RP or cone-rod dystrophy,
with promising results (53-55) . The history starts to be written
in this very promising therapeutic field. Welcome!
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